The long-term goal of this research is to elucidate the biochemical mechanisms by which heme compounds and bile pigments are synthesized in mammalian systems, and to define the variables which control some of the individual steps in the sequence. Investigations will concentrate on the building up of monopyrrole units to form the tetrapyrrole ring, and the subsequent modifications of side chains of the tetrapyrrole nucleus. Later studies may investigate cleavage of the Fe-tetrapyrrole ring to form the open chain bile pigments. The enzymes which catalyze the synthetic steps to heme will be obtained from erythropoietic mouse spleen, because this organ is analogous to bone marrow in its physiology and biochemistry. It is hoped that the knowledge obtained will be relevant to a number of human disorders associated with porphyrinuria or hyperbilirubinemia.